Microtubules are conserved cytoskeletal elements that form by the polymerization of alpha- and beta-tubulin heterodimers. The formation of polymerization-competent alpha- and beta-tubulin heterodimers requires that alpha-tubulin and beta-tubulin be properly folded. Specific cofactors are required for the folding of alpha- and beta-tubulin in vitro and homologs of these cofactors have been found in numerous organisms, including S.cerevisiae (reviewed in 6).

CIN4 is a non-essential gene that encodes a small GTPase of the ras superfamily, ADP-ribosylation factor (ARF) subfamily (4). The human homolog of CIN4, Arl2, has been shown to regulate the activity of the post-chaperonin tubulin folding pathway, in part by decreasing the affinity of cofactor D (Cin1p inS.cerevisiae) for native tubulin (4). By analogy, CIN4 may play a similar regulatory role in the yeast cofactor pathway, as it genetically interacts with several of the yeast tubulin cofactors (e.g. PAC2/cofactor E, CIN1/cofactor D, CIN2/cofactor C) (1, 7), and interacts in the two-hybrid assay with Cin2p/cofactor C (7).

CIN4 was isolated in a genetic screen for mutants that display super-sensitivity to benomyl, a microtubule-depolymerizing drug (1), and was independently isolated in a genetic screen for elevated chromosome loss (3). cin4 null mutants are cold-sensitive, show synthetic phenotypes in combination with tubulin mutants (1) and have defects in nuclear migration and nuclear fusion (or karyogamy) (3).

Last updated: 2003-08-28